New case detection rates in leprosy remain obstinately high despite years of global coverage with multiple drug therapy (MDT) and a major decrease in prevalence. This fact demonstrates clearly that treatment alone does not block transmission of leprosy and underscores major gaps in our comprehension of the disease;we do not know how leprosy is transmitted and we have not fully developed or assessed promising tools for detecting preclinical leprosy, a possible source of transmission, or tracing individual isolates within communities. Under previous support, this consortium identified Mycobacterium leprae specific proteins and peptides, promising in cell mediated immune assays in leprosy endemic regions, and sufficient genetic diversity within M. leprae genomes to trace individual isolates, globally and locally. The continuing development of these tools in leprosy endemic regions of Brazil, and subsequently through the newly formed IDEAL (Initiative for Diagnostic and Epidemiological Assays for Leprosy) global network, to address transmission and early diagnosis, are the major foci of the proposed research. Also, as biomarkers for disease susceptibility, notably nerve damage and disability, both protective and disease inducing cytokines will be determined with the aim of identifying antigens able to induce a discriminating T cell phenotype in leprosy patients compared to controls. This program, the culmination of a career in basic research, will bring to leprosy control programs the means to assess the effects of chemotherapeutic intervention on disease incidence, and point the way to eradication of a disease that afflicts the most impoverished of humanity.